In recent years, a large class of proteins has been discovered that is characterized by the presence of one or more sequences that approximate the form (Tyr,Phe)-X-Cys-X2,4-Cys-X3-Phe-X5-Leu-X2-HisX3,4-His where X represents relatively variable amino acids. Each of these sequences appears to form an independent structural domain organized around a zinc ion bound to the cysteine and histidine residues. The proteins in this class (often referred to as zinc finger proteins) appear to bind DNA in a site specific manner via the zinc-binding domains. By virtue of this DNA binding activity and accompanying effects of transcription, these proteins seem to play central roles in developmental control processes and in cancer as evidenced by the discovery that proteins associated with Wilm's tumor and certain gliomas are zinc finger proteins. A great deal has been learned in the past four years about the structure and metal-binding properties of single zinc finger domains. However, tandem arrays of these domains are required for activity. The metal-binding properties of a tandem array will be studies with the goal of determining if adjacent units bind metals in cooperative fashion. The DNA-binding properties of a representative protein will be studies to determine which amino acids are involved in direct interactions with the DNA binding site. The results of these studies should allow discrimination between current models for zinc finger protein-DNA complexes and may lead to the development of general rules that relate the amino acid sequence of a zinc finger protein and the nucleotide sequence of its binding site. Finally, new methods for sequence of a zinc finger protein and the nucleotide sequence of its binding site. Finally, new methods for isolating genes that encode tandem arrays of these domains will be developed. It is clear from currently available information that most eukaryotic genomes contain tens to hundreds of different zinc finger proteins so that methods for rapidly isolating zinc finger genes could be quite useful in a variety of systems. Taken together, the results of these studies will provide important insights into the potential roles zinc might play in regulating the properties of these proteins in vivo, into the structural mechanisms that these proteins use in recognizing specific DNA sequences, and into the biological processes these proteins are involved in regulating.